Our overall objective is to determine whether the combination of hyperthermia and x-ray can offer a therapeutic advantage over x-irradiation alone in a murine host-tumor model, and to determine what conditions will optimize that advantage. The specific goals of the project will be to: 1) Determine the effect of multiple fraction treatments with heat following x-irradiation on a rapidly proliferating normal tissue, the jejunal epithelium (LD50/6 and crypt cell survival assays), and the late effects on a slowly-turning-over normal tissue, the spinal cord (50% myelitis dose as measured by hind leg dysfunction). 2) Evaluate the effect of multiple fraction treatments with heat following x-irradiation on two established lines of C3H mouse mammary tumors. The growth delay (time to return to treatment volume) and the local control dose (TCD 50/120) will be determined for the slow-growing (Slow line) and fast-growing (S102F line) mammary tumors. Comparing the results above, the effect of fractionation on therapeutic gain will be determined. 4) Utilizing the fractionated treatment assays, the effect of variation of the interval between x-irradiation and heat, and of alteration of the interval between fractions, on therapeutic gain will be evaluated. The information gained from this study will provide a foundation for the design of clinical hyperthermia protocols having the maximum probability of selective hyperthermic radiosensitization of tumor relative to both acute and chronic normal tissue damage.